Synovial Biomarker Modulation and Clinical Response to Umbilical Cord-Derived MSC Treatment in Knee Osteoarthritis: A...

ObjectiveUmbilical cord-derived mesenchymal stromal cells (UC-MSCs) are a promising treatment for knee osteoarthritis (KOA). This study aimed to (1) characterize early synovial fluid biomarker changes after intra-articular UC-MSCs therapy in advanced KOA and (2) explore their relationship with short-term clinical outcomes.MethodsIn this prospective, single-arm case series, 15 patients with advanced KOA (Kellgren-Lawrence III-IV) scheduled for total knee arthroplasty received a single intra-articular injection of 20 × 10⁶ allogeneic UC-MSCs. Synovial fluid was aspirated at baseline and approximately 6 weeks post-injection. A panel of 29 soluble biomarkers related to inflammation, matrix remodeling, immune signaling, angiogenesis, and metabolism was quantified using multiplex immunoassays. Clinical status was evaluated with Patient-Reported Outcome Measures (PROMs) before and at a mean of 48 ± 18 days after the injection. Paired differences were analyzed using the Wilcoxon signed-rank tests.ResultsSignificant post-treatment differences were observed in biomarkers associated with extracellular matrix turnover (Matrix Metalloproteinase [MMP]-1, MMP-3, MMP-7, Cartilage Oligomeric Matrix Protein [COMP]), vascular remodeling (Vascular Endothelial Growth Factor [VEGF], Vascular Cell Adhesion Molecule [VCAM]-1), immune modulation (interleukin [IL]-8), and metabolic or structural regulation (Leptin, dickkopf [Dkk]-1). Most PROMs demonstrated significant improvements. These findings describe molecular changes in synovial fluid observed after intra-articular UC-MSC administration.ConclusionsIn this prospective single-arm cohort, intra-articular UC-MSC administration was feasible and well tolerated, and we observed pre-post changes in synovial fluid biomarkers and patient-reported outcomes. These findings do not establish causality and warrant confirmation in controlled studies. The study was registered at Clinicaltrials.gov: Mechanisms of Treatment Effects Using Cultured, Allogeneic Mesenchymal Stromal Stem Cells (MSCs) in Knee Osteoarthritis, NCT06078059, https://clinicaltrials.gov/study/NCT06078059?intr=NCT06078059.